The Human Immunodeficiency Virus (HIV-1) packages its genome by specific interactions between the nucleocapsid (NC) domain of Gag and an approximately 120 nucleotide region of the unspliced viral RNA, known as the psi-site, located between the 5' LTR and the gag initiation site. The HIV-1 psi-site contains four stem loop structures designated SL1 through SL4 connected by relatively short linkers; all stem loops are required for efficient encapsidation. Genome packaging is an essential step in the life cycle of HIV-1; furthermore, there is increasing evidence that RNA encapsidation appears to be dependent on a higher order RNA structure. The goal of the proposed research is to gain insight into the structural determinants of genome packaging in HIV-1 by structurally characterizing the psi-RNA packaging element using nuclear magnetic resonance (NMR) spectroscopy. Knowledge of the three dimensional structure of the psi-RNA packaging element will provide information I about the structural details of genome recognition and encapsidation in HIV-1, which may in turn lead to advances in AIDS therapeutics.